title: IL-21 is pivotal in determining age-dependent  effectiveness of immune responses  in a mouse model of human hepatitis B.
abstract: HBV is a noncytopathic hepadnavirus and major human pathogen that causes immune-mediated acute and chronic hepatitis. The immune response to HBV antigens is age dependent: viral clearance occurs in most adults, while neonates and children usually develop chronic infection and liver disease. Here, we characterize an animal model for HBV infection that recapitulates the key differences in viral clearance between early life and adulthood and find that IL-21 may be part of an effective primary hepatic immune response to HBV. In our model, adult mice showed higher HBV-dependent IL-21 production in liver, compared with that of young mice. Conversely, absence of the IL-21 receptor in adult mice resulted in antigen persistence akin to that of young mice. In humans, levels of IL-21 transcripts were greatly increased in blood samples from acutely infected adults who clear the virus. These observations suggest a different model for the dichotomous, age dependent outcome of HBV infection in humans, in which decreased IL-21 production in younger patients may hinder generation of crucial CD8+ T and B cell responses. These findings carry implications for therapeutic augmentation of immune responses to HBV and potentially other persistent liver viruses.
authors.affiliation: Department of Medicine, UCSF, San Francisco, California, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Publicover
authors.forename: Amanda
authors.initials: A
authors.lastname: Goodsell
authors.forename: Stephen
authors.initials: S
authors.lastname: Nishimura
authors.forename: Silvia
authors.initials: S
authors.lastname: Vilarinho
authors.forename: Zhi-en
authors.initials: ZE
authors.lastname: Wang
authors.forename: Lia
authors.initials: L
authors.lastname: Avanesyan
authors.forename: Rosanne
authors.initials: R
authors.lastname: Spolski
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: Stewart
authors.initials: S
authors.lastname: Cooper
authors.forename: Jody L
authors.initials: JL
authors.lastname: Baron
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006509:Hepatitis B / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D007249:Inflammation; D007378:Interleukins / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D000098546:Interleukin-21
chemical_list: D000941:Antigens; D007378:Interleukins; D000098546:Interleukin-21